Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma.

PURPOSE

A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma.

METHODS

Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU.

RESULTS

Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate.

CONCLUSIONS

The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.